title: Comparison of once- versus twice-daily administration of insulin detemir, used with mealtime insulin aspart, in basal-bolus therapy for type 1 diabetes: assessment of detemir administration in a progressive treat-to-target trial (ADAPT).
abstract: OBJECTIVE
  The purpose of this study was to compare effects of insulin detemir once daily versus twice a day in a basal-bolus insulin regimen.
  
  
  METHODS
  In this open-label, 7-month study, 520 patients with type 1 diabetes were randomly assigned to receive detemir once daily or twice daily with mealtime insulin aspart. Insulin doses were titrated over 1 month, with patients followed up over the subsequent 3 months. Thereafter, patients were able to switch from one regimen to the other, with an additional nonrandomized 3-month follow-up, to a total of 7 months. The primary end point was A1C at 4 months, with noninferiority defined as a difference <0.4% between groups.
  
  
  RESULTS
  A1C at 4 months was 8.1 +/- 0.9 versus 8.0 +/- 1.0% with once- and twice-daily detemir, respectively, with an adjusted between-group difference of 0.12% (95% CI -0.01 to 0.25%), showing noninferiority for once-daily dosing. Similar results were found in the per protocol population. Improvement in A1C was similar in both groups (-0.4 +/- 0.8 vs. -0.5 +/- 0.8%; P = 0.09, NS) but with differences in the 7-point glucose profile. Detemir doses were lower (29 +/- 18 vs. 39 +/- 20 units/day, P < 0.001), but aspart doses were higher (34 +/- 17 vs. 26 +/- 14 IU/day, P < 0.001) with once-daily detemir. At 7 months, A1C decreased slightly in patients switched from once-daily to twice-daily administration (8.2 +/- 0.8 vs. 8.0 +/- 0.8%; P = 0.34, NS) in association with increased total insulin doses (P < 0.05), but A1C increased in those switched from twice-daily to once-daily administration (7.2 +/- 0.9 vs. 7.6 +/- 0.8%, P < 0.05) in association with decreased doses (P < 0.05).
  
  
  CONCLUSIONS
  Although some individuals may benefit from twice-daily dosing, the most suitable routine starting schedule for detemir in a basal-bolus regimen for type 1 diabetes is once-daily injection.
authors.affiliation: Medical Clinic, Villecresnes, France. jplefloch@dietvill.com
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Le Floch
authors.forename: Marc
authors.initials: M
authors.lastname: Lévy
authors.forename: Helen
authors.initials: H
authors.lastname: Mosnier-Pudar
authors.forename: Frank
authors.initials: F
authors.lastname: Nobels
authors.forename: Sylvie
authors.initials: S
authors.lastname: Laroche
authors.forename: Sophie
authors.initials: S
authors.lastname: Gonbert
authors.forename: Eveline
authors.initials: E
authors.lastname: Eschwege
authors.forename: Pierre
authors.initials: P
authors.lastname: Fontaine
mesh_terms: D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism*; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy*; D004334:Drug Administration Schedule; D004435:Eating; D005500:Follow-Up Studies; D006442:Glycated Hemoglobin / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D061267:Insulin Aspart / Q000008:administration & dosage / Q000627:therapeutic use*; D000069057:Insulin Detemir; D049528:Insulin, Long-Acting / Q000008:administration & dosage / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D001786:Blood Glucose; D006442:Glycated Hemoglobin; D061267:Insulin Aspart; D000069057:Insulin Detemir; D049528:Insulin, Long-Acting